Mass analyzers are used to analyze solid, liquid, and gaseous samples by measuring the mass-to-charge (m/z) ratio of ions produced from a sample in an ion source. Many types of ion sources operate at relatively high pressure, that is, higher than vacuum pressure required by the mass analyzer and/or detector. For example, some types of ion sources operate at or near atmospheric pressure, such as electrospray (ES), atmospheric pressure chemical ionization (APCI), inductively coupled plasma (ICP), and atmospheric pressure (AP-) MALDI and laser ablation ion sources. Other types of ion sources operate at intermediate vacuum pressures, such as glow discharge or intermediate pressure (IP-) MALDI and laser ablation ion sources. Still other types of ion sources are configured in a vacuum region in which the vacuum pressure may increase during operation of the ion source, such as electron ionization and chemical ionization ion sources.
Ion sources operated at higher pressures are usually configured to deliver ions into the vacuum region of the mass analyzer via one or more differential pumping vacuum stages that isolate the mass analyzer and detector from the higher pressure of the upstream stages. In such configurations, an ion optical arrangement is typically configured between the ion source and the mass analyzer entrance in order to facilitate transfer of ions from the ion source to the mass analyzer entrance through the multiple vacuum pumping stages, while restricting the flow of background gas into the mass analyzer region.
Apart from efficiently transferring ions from the ion source to the mass analyzer, such ion optical arrangements are also often configured to prevent background particles originating in the ion source from reaching the mass analyzer detector, where they would produce background noise in the mass spectra. Depending on the type of ion source, such particles may include photons, undesolvated cluster ions and neutral species, electrons, and charged and uncharged aerosol particles. Such particles may not be effectively eliminated by the mass analyzer, if at all, in which case they may produce background noise in the recorded mass spectra, thereby limiting the achievable signal-to-noise ratio. Consequently, depending on the type of ion source employed and the instrument configuration, various approaches to preventing such background particles from reaching the mass analyzer detector have been devised.
One approach that is now common practice is to locate the detector outside the field of view from the ion source, as described, e.g., in Dawson, “Quadrupole Mass Spectrometry and Its Applications”, pp. 34-35 and 138-139. In these so-called ‘off-axis’ detector configurations, most photons and neutral species emanating from the ion source follow flight paths that miss the detector, while mass analyzed ions of interest are deflected with electric fields to intersect with the detector. Most of these configurations consist simply of misaligning the detector with the exit of the mass analyzer, possibly combined with some electrostatic deflector for steering ions to the detector. However, relatively complicated versions of such arrangements were also proposed, for example, by Brubaker in U.S. Pat. No. 3,410,997, in which curved ion guides were configured to transport the mass-analyzed ions from the exit of a quadrupole mass analyzer to a detector.
It is usually more advantageous, however, to remove undesirable particles from the ion path before they enter the mass analyzer. One reason for this is that the impingement of such particles on surfaces in the mass analyzer may result in the buildup of an electrically insulating layer of contamination on surfaces, which may accumulate charge that distorts electric fields and degrade performance. Another reason is that the impact of such particles on surfaces may create secondary particles which may, in turn, find their way to the mass spectrometer detector and create noise. Hence, for example, Brubaker further described in U.S. Pat. No. 3,473,020 a number of arrangements in which curved ion guides are configured before the entrance to a quadrupole mass filter, whereby ions of interest are guided to the mass filter entrance, while photons and neutral species proceed undeflected and thus do not enter the mass filter.
A number of alternative configurations have since been developed with at least one of the objectives being to prevent background particles originating with the ion source, such as photons, neutrals, charged droplets, etc., from reaching a mass analyzer detector. For example, Mylchreest et al. describe in U.S. Pat. No. 5,171,990 apparatus and methods for preventing high velocity droplets or particles, emanating from a capillary orifice into vacuum from an atmospheric pressure ion (API) source, from proceeding into the lens region at the entrance of a mass analyzer. Essentially, Mylchreest et al. describe orienting the capillary so that its axis is offset from a skimmer orifice or aperture separating the capillary exit vacuum region from the vacuum region of the mass analyzer entrance lens. Hence, high velocity droplets and particles traveling along the axis of the capillary are blocked from proceeding into the mass analyzer region, while ions of interest are deviated from the axis to travel through the orifice or aperture by virtue of their free jet expansion from the capillary exit. However, such a configuration would suffer from contamination buildup on the orifice or aperture, leading to unstable operation due to electrostatic charging. Also, the transmission efficiency of ions would degrade due to scattering of ions out of the deviated flight path from background gas molecules in this relatively high pressure region.
Takada et al. describe in U.S. Pat. No. 5,481,107 the incorporation of an electrostatic lens disposed between an API source and the entrance to a mass analyzer. The mass analyzer axis and that of the ion source and interface optics is offset so as to prevent droplets and neutral species from proceeding past the entrance aperture of the mass analyzer, while the electrostatic lens is configured to re-direct ions of interest from the axis of the ion source and interface optics into the mass analyzer entrance aperture. One difficulty with such an arrangement is that ions entering vacuum via such AP/vacuum interfaces typically exhibit similar velocity distributions, more or less independent of their mass. This results in ion kinetic energies that depend strongly on ion mass, and, because the focusing action of electrostatic lenses in vacuum depends only on ion kinetic energy and ion charge, and not ion mass, such a configuration leads to severe mass discrimination effects.
Mordehai et al. describe in U.S. Pat. Nos. 5,672,868, 5,818,041, and 6,069,355, configurations in which a multipole RF ion guide is located between an ion source and the entrance to a mass analyzer. Ions are transported from the ion source to the input end of the ion guide along an axis that is at an angle with respect to the axis of the ion guide. The ions enter the input end of the ion guide while they are entrained in an aerodynamic jet emanating from the ion source, or from an ion transport device such as a capillary. Ions entering the input region of the ion guide are re-directed to move along the ion guide axis via the action of the RF fields in the ion guide, and are transported by the ion guide to the entrance of the mass analyzer. Neutral and energetic charged particles continue more or less along their original trajectories and are lost to the surrounding surfaces. However, as with the apparatus and methods of Takada et al. '107, described above, ions entrained in an aerodynamic jet have ion kinetic energies that depend on ion mass. Hence, the re-directing of ions by the RF fields in the ion guide with good efficiency requires that the ions be quickly collisionally cooled by collisions with background gas molecules, which is increasingly more important the greater the ion mass, hence ion energy. Hence, Mordehai et al. provide a separate gas inlet to let in extra ‘buffer’, or collision, gas for this purpose. Because the ion guide is located entirely within a single vacuum stage, the gas pressure would not be substantially different from one end of the ion guide to the other end. Hence, the probability of collisions between ions and background gas molecules as ions exit the ion guide would have to be substantial in the apparatus of Mordehai et al., resulting in degraded transport efficiency in this region. Such scattering is also known to lead to increased background noise at the detector, due to the acceleration of scattered ions in the RF fringe fields in this region, as well as the production of energetic neutral species due charge-exchange neutralization of such accelerated ions (as discussed below).
Wells describes in U.S. Pat. No. 6,730,904 a multipole ion guide that is configured in segments, where different segments may be operated with independent voltages. This allows ions traversing the ion guide to be guided along different optical axes within the ion guide from one segment to the next, where the different axes are offset with respect to each other. Wells describes such segmented ion guide configurations in which ions and neutral particles enter the ion guide along an entrance axis, and the ions are then guided so as to exit the ion guide along an exit axis that is offset from the entrance axis. The neutrals proceed along the entrance axis direction and are thereby prevented from proceeding past the ion guide exit. Again, the efficiency of ion transport depends on collisionally cooling energetic ions as they enter the ion guide. For example, Wells demonstrates through computer simulations of one embodiment that many more ions are lost to the ion guide electrodes when the gas pressure in the ion guide is reduced from a pressure corresponding to a mean free path of 1 mm to a pressure corresponding to a mean free path of 10 mm. Hence, as with the apparatus and methods described by Mordehai et al., as discussed above, a significant background gas pressure is expected in the region where ions exit the ion guide, resulting in collisions between ions and background gas molecules in this region, which ultimately leads to increased background noise at a downstream detector.
In European Patent Application 0 237 259 A2, Syka describes tandem quadrupole mass spectrometer configurations, some of which include a bent or tilted quadrupole ion guide positioned just before the final quadrupole mass analyzer and detector. The bent or tilted quadrupole ion guide is described to reduce noise by preventing excited and fast neutral particles and fast ions emanating from an ion source from reaching the detector, because the tilted or bent quadrupole removes the detector from line-of-sight of the ion source. The entrance and exit ends of such bent quadrupole ion guide reside in the same vacuum stage limiting the ions within the bent quadrupole ion guide to traverse a single background pressure region constrained by the single vacuum stage pumping speed.
Kalinitchenko describes in U.S. Pat. No. 6,614,021 a configuration of an ICP/MS instrument that incorporates an electrostatic mirror between an ICP ion source and a quadrupole mass analyzer. The mirror provides an electrostatic focusing field that deflects ions from the ion source, for example, by 90 degrees, and focuses them through an aperture at the entrance of the quadrupole mass analyzer. Such an arrangement avoids any line-of-sight from the ion source to the detector, thereby preventing background particles originating in the ion source, such as photons and energetic neutral species, from reaching the detector. Kalinitchenko reports a substantial increase in sensitivity relative to prior art, measured as counts/sec per parts-per-million (ppm) of analyte. However, the increase was achieved “without attendant increase in background” noise, implying that significant background noise persisted as in previous configurations, in spite of the reflecting mirror.
All of the prior art discussed above describe apparatus and methods to reduce or eliminate background noise caused primarily by undesirable particles emanating from an ion source. However, it is now appreciated that background particle noise can also originate from other sources besides the ion source. For example, while the reflecting mirror arrangement of Kalinitchenko described in U.S. Pat. No. 6,614,021, discussed above, provided for no possible line-of-sight between the ion source and the detector, the significant background noise that was previously observed nevertheless persisted, demonstrating that such background particle noise must in fact originate from processes separate from the ion source itself. The observed non-source-related background noise was reduced substantially, as described subsequently by Kalinitchenko in U.S. Pat. No. 6,762,407, by incorporating a set of curved, or tilted, ‘fringe’ electrodes between the entrance of the quadrupole mass analyzer and the quadrupole entrance aperture. Kalinitchenko suggests that energetic neutral particles are produced as ions are accelerated through residual gas in the apparatus. That is, some ions inevitably interact with background gas molecules, for example, via resonant charge exchange processes, resulting in conversion of the accelerating ions into energetic neutral species. Another possible explanation is that such acceleration leads to some degree of ion fragmentation, resulting in energetic neutral fragments that are on a favorable trajectory to reach the mass analyzer detector.
Kalinitchenko further describes that such collisions occur not only during acceleration of ions along their axial motion direction, such as in the reflecting mirror region, but also along directions orthogonal to their axial direction, for example, in the fringe fields between the end of an RF multipole ion guide and an aperture proximal to the end. Hence, the curved or tilted ‘fringe’ electrodes described by Kalinitchenko in the '407 patent prevented energetic neutrals created in the electrostatic mirror vacuum region, and in the region of the entrance aperture and the upstream section of the ‘fringe’ electrode structure, from reaching the detector.
On the other hand, it is well known that the interactions between ions and background gas molecules involve not only the neutralization of the ions, but also scattering of ions out of the beam path, resulting in additional ion loss. Ion losses also occur due to scattering by oscillating fringe fields proximal to the entrance or exit of an RF multipole ion guide. In any case, the ion transmission efficiency in the apparatus and methods described in the '407 patent by Kalinitchenko would be reduced due to ions lost by scattering with background gas molecules as they move from the relatively higher background pressure vacuum region of the reflecting mirror, through the vacuum interface aperture, and traverse the region between the interface aperture and the RF ‘fringe’ field electrodes.
The loss of ions due to scattering with background gas molecules in vacuum regions of higher background gas pressure is frequently minimized by transporting ions through such regions within an RF multipole ion guide. The RF fields within such ion guides generate an effective repelling force directed orthogonally to the ion beam direction, that is, orthogonal to the ion guide axis, thereby counteracting such scattering out of the beam path. Further, such collisions serve to dampen the ions' kinetic energy, which allows the ions to settle closer to the ion guide axis, thereby improving transport efficiency. However, significant scattering losses nevertheless occur when ions must exit the ion guide in a region where collisions with background gas molecules are likely. This is a problem typically encountered in conventional multiple vacuum stage vacuum systems, in which static electric field vacuum partitions separate the different vacuum stages. Ions traveling within an ion guide through one vacuum stage with a relatively higher vacuum pressure must exit the ion guide and traverse an aperture provided in the vacuum partition to move into the next vacuum stage that has a lower gas pressure, with such conventional vacuum stage configurations. Ions are lost due to scattering in collisions with background gas molecules once they exit the ion guide, and ions are also lost due to scattering by fringe fields between the aperture and the ion guide exit in the upstream vacuum stage, or between the aperture and the ion guide entrance in the downstream vacuum stage. Even if the gas pressure in the next vacuum stage is low enough, on average, that collisions between ions and gas molecules are rare, nevertheless, ions may experience frequent collisions with gas molecules that flow from the upstream, higher background gas pressure vacuum stage into the lower pressure downstream vacuum stage in the vicinity to the interface aperture.
The problem of ion loss during transit between vacuum stages has been effectively addressed by Whitehouse, et al. in U.S. Pat. Nos. 5,652,527; 5,962,851; 6,188,066; and 6,403,953, which describe extending an RF multipole ion guide through the vacuum partitions between two or more vacuum stages. Essentially, these patents describe RF multipole ion guides that effectively transport ions through and between vacuum stages at high and low background gas pressures, and are configured with a small enough cross-section to act as an effective restriction to gas flow between vacuum stages, similar to an aperture or orifice in a vacuum partition. Whitehouse et al. further describes in these documents the incorporation of multipole ion guides extending through multiple vacuum pumping stages between API sources and mass analyzers.
This same situation also exists at the entrance and exit of a conventional collision cell, in which a multipole ion guide is located in a region of gas pressure that is high enough so that ions collide with background gas molecules as they traverse the ion guide. Although ions are prevented from scattering out of the beam path by the RF fields of the ion guide while traversing the ion guide, the ions typically must enter and exit the ion guide via apertures at the ends of the collision cell that help maintain a pressure differential between the region internal to the collision cell and vacuum regions external to the collision cell. Hence, ions are scattered by collisions with collision gas molecules as the ions enter and leave the collision cell, resulting in ion losses. Furthermore, background particles in the form of energetic neutral species may be created as a result of ions being accelerated into the collision cell for the purpose of collision-induced fragmentation. Some of these energetic neutral species may continue through the exit of the collision cell, and into a mass analyzer and detector located downstream, thereby creating background particle noise. Furthermore, ions exiting the collision cell must pass through the RF fringe fields between the ion guide exit end and the exit aperture of the collision cell. This is also a region where collisions between ions and gas molecules occur, resulting in ion scattering losses, as well as ion neutralization via charge exchange, for example. As discussed above, it is known that ions may be accelerated to higher energies in such RF fringe fields, and neutralization of energetic ions creates energetic neutral species, which then also may continue on downstream to create background noise in a mass analyzer and detector.
The problem of ion loss during ion transit into and out of a conventional collision cell has also been addressed by Whitehouse, et al. in U.S. Pat. No. 7,034,292, which describes configurations that include a multipole ion guide that extends continuously from inside a collision cell to outside the collision cell, where the multipole ion guide terminates in a region of background pressure that is low enough that collisions between ions and background gas molecules essentially do not occur. In such configurations, ions do not experience RF fringe fields until they are in a vacuum region with low enough background gas pressure that collisions with background gas molecules essentially do not occur. Nevertheless, energetic neutral species that are created by collisions between ions and collision gas molecules as the ions are accelerated into the collision cell remain a potential source of background particle noise at a mass analyzer detector located downstream of the collision cell.
In all of the configuration described by Whitehouse in U.S. Pat. Nos. 5,652,527; 5,962,851; 6,188,066; 6,403,953; and 7,034,292, multipole ion guides were configured to be in axial alignment between the ion source and the entrance to a mass analyzer. In other words, no provision was made for preventing background particles emanating from an ion source, or created along the beam path from collisions with background gas molecules, from entering a mass analyzer or from reaching a mass analyzer detector. Hence, there has not been available a solution to the problem of providing efficient transport of ions between a region of higher background gas pressure, at which collisions between ions and background gas molecules occur, and a region of lower background gas pressure, at which such collisions essentially do not occur, while simultaneously preventing background particles originating either from an ion source, and/or created in collisions between ions and background gas molecules during ion transit, from reaching a mass analyzer detector and thereby causing background noise in mass spectra.